Mesenchymal stem cells ameliorate atherosclerotic lesions via restoring eNOS activity and relaxation response in endothelial cells

• Main Authors: Yu-Ling Lin, 林育玲
• Other Authors: Shih-Chieh Hung
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/43826311211647901986

碩士 === 國立陽明大學 === 臨床醫學研究所 === 101 === Objectives The purpose of the study was to evaluate the effect of mesenchymal stem cells (MSC) to treat atherosclerosis in apoE−/− mice. Background Transplantation of MSCs has been proved to be beneficial in treating myocardial infarction (MI), but the ability of MSCs to ameliorate pre-clinical atherosclerosis remains unknown. Methods In vitro, oxLD-induced human umbilical vein endothelial cells (HUVEC) damage was used. The Akt/eNOs expression was analyzed by western blot. Nitric oxide(NO) production was analyzed by Griess Assay. PCR array analysis was used to search for the possible factor in the effect of MSC. In vivo, groups with MSC, MSC treated with anti-macrophage inflammatory protein 2 (MIP-2) Ab, MIP-2 alone and PBS were studied in apoE −/− mice. Endothelial function was determined by tension recording test. Akt/eNOs expression was quantified by Immunohistochemistry. Results MSC reversed the inhibitory effect of oxLDL on Akt pathway, thereby restoring eNOS activity and ameliorating endothelial dysfunction in apoE−/− mice. The improvement of endothelial dysfunction by MSCs was significantly blocked in the group of MSCs treated with anti-MIP-2 Ab and improved by MIP-2 injection alone. Among the mitogen-activated protein kinases(MAPK) family, the level of phosphorylated P38 was increased in MSCs upon exposure to oxLDL. The effect of MSC p38 knockdown on oxLDL-exposure MSC also significantly inhibited IL-8 expression. Conclusions: MSC transplantation improved the endothelial function and plaque formation in apoE−/− mice. IL-8 and the P38 MAPK signaling pathway are involved in the protective effect of MSCs. The study contributes to elucidate the mechanisms in the use of MSCs for atherosclerosis.